Neisseria gonorrheae and N. meningitidis share many properties, although these two species are associated with distinct clinical spectra of disease. N. gonorrhoeae is the causative agent of the sexually transmitted disease gonorrhea. N. meningitidis causes epidemics of meningitis, as well as less frequent endemic infections. The genes or gene products responsible for the dramatically different infections caused by these closely related bacteria have not been identified. Studies on the pathogenesis of neisserial infections and application of the most powerful genetic and molecular approaches to those studies will be facilitated by knowledge about the organization of genes on the chromosomes of these organisms. The gonococcus and meningococcus also provide systems in which to study the organization, evolution, and function of repeated genes and sequence elements, which are unusually abundant in these species. The long-range goal of this project is to characterize the organization of gonococcal and meningococcal genomes, to identify genes unique to each species that are important in determining the type of infection caused, and to determine if genome organization is influenced by the frequent recombinational events and horizontal genetic exchange occurring in these species. Macrorestriction maps of one strain each of N. gonorrhoeae and N. meningitidis have been constructed. Comparing the arrangements of genetic loci in the two strains revealed complex genomic rearrangements between them, particularly in one 500 kb region of the chromosome. The location of rRNA operons on the chromosomes of different gonococcal and meningococcal strains also varies, suggesting that major chromosomal rearrangements in these species are relatively common. The Specific Aims are: 1) Characterize the intra-species and inter-species differences in chromosome organization among gonococcal and meningococcal strains, determining the extent of rearranged segments and identifying the specific sequences that provide the endpoints for rearrangement. 2) Identify differences in the genomes of N. gonorrhoeae and N. meningitidis by cloning and mapping genes unique to the gonococcus that are absent in the meningococcal genome. 3) Continue to provide a mapping resource for the Neisseria research community, determining the physical relationships among newly identified genetic loci or rearranged loci for other investigators.